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Objectives: This study aimed to identify facilitators and barriers to parent-child communication in pediatric palliative care, providing insights for medical professionals developing targeted interventions to enhance parent-child communication and improve its effectiveness. Methods: Whittemore and Knafl’s integrative review method was employed to guide a systematic search for literature in six databases (Medline, Embase, CINAHL Complete, PsycINFO, Web of Science, and Cochrane Library). Peer-reviewer articles published in the English language from inception to December 2023. All of the identified studies were screened, extracted, and analyzed independently by two researchers. Results: Twenty-four articles were included. The findings of the relevant studies were analyzed using thematic analysis. Four themes were identified as facilitators: legacy-making, resilience training programs, guidance from the healthcare team, and positive communication. Seven themes were identified as barriers: denial, being unprepared and evasive, mutual protection, being overwhelmed by painful emotions and overloaded with information, incorrect views of medical professionals and parents, negative communication, and cultural context. Conclusions: Parents and professionals should avoid myths about protecting the child and encourage open communication that respects the child’s wishes. The specialized pediatric palliative care team should carefully monitor parent-child communication, determine if any obstacles exist, and design more interventions to enhance it.

Abstract RGS (Regulator of G protein signaling) proteins have long captured the fascination of researchers due to their intricate involvement across a wide array of signaling pathways within cellular systems. Their diverse and nuanced functions have positioned them as continual subjects of scientific inquiry, especially given the implications of certain family members in various cancer types. Of particular note in this context is RGS20, whose clinical relevance and molecular significance in hepatocellular carcinoma we have recently investigated. These investigations have prompted questions into the prevalence of pathogenic mutations within the RGS20 gene and the intricate network of interacting proteins that could contribute to the complex landscape of cancer biology. In our study, we aim to unravel the mutations within the RGS20 gene and the multifaceted interplay between RGS20 and other proteins within the context of cancer. Expanding on this line of inquiry, our research is dedicated to uncovering the intricate mechanisms of RGS20 in various cancers. In particular, we have redirected our attention to examining the role of RGS20 within hematological malignancies, with a specific focus on multiple myeloma and follicular lymphoma. These hematological cancers hold significant promise for further investigation, as understanding the involvement of RGS20 in their pathogenesis could unveil novel therapeutic strategies and treatment avenues. Furthermore, our exploration has extended to encompass the latest discoveries concerning the potential involvement of RGS20 in diseases affecting the central nervous system, thereby broadening the scope of its implications beyond oncology to encompass neurobiology and related fields.

Abstract Objective To identify factors that influence the severity of tinnitus via a hierarchical multiple linear regression model. Methods The study was a retrospective cross‐sectional analysis. The study included 331 patients experiencing tinnitus as their primary concern, who visited Shanghai Changzheng Hospital of the Navy Medical University between 2019 and 2021. Data on general health status and disease characteristics were collected from all patients. With their consent, participants underwent audiological evaluatons and completed questionnaires to analyze the characteristics of their tinnitus and the factors influencing its severity. Results The correlation analysis showed a positive relationship between tinnitus frequency, tinnitus loudness, SAS scores, and PSQI scores with THI scores (P

The topmouth culter (Culter alburnus) is at the top of the food chain and plays an important role in the maintenance of freshwater ecosystem stability. It is also a commercially important aquaculture fish species in China. To establish conservation strategies and breeding programs, a total of 16 polymorphic microsatellite loci were isolated from transcriptome-derived sequences of C. alburnus. Characterization of these loci was assessed against 1 wild and 3 cultured populations in Huzhou, China. The number of alleles per locus ranged from 3 to 10 with an average of 5.25. A bottleneck effect was observed in all 4 populations; The ChangXing population showed moderate genetic differentiation when compared with other populations (FST values, 0.0695–0.0788). The microsatellite loci would be useful for further studies on population genetic diversity, genetic structure, and assessments of the artificial propagation release effect of C. alburnus.

As a result of significant advances in geophysics, we have developed a rich arsenal of geophysical methods to infer the internal structure of the Earth. However, the method we could use to infer the internal structure of celestial bodies other than the Earth are still very limited, often relying on geodetic data from orbital probes, landers and astronomical observations. Among these geodetic method, solid tides are of great importance for the study of the celestial bodies' internal structure. Solid tidal deformation and the tidal dissipation provide key information about the internal structure of the rocky celestial bodies, especially the deep structure which contains core-mantle boundary and core. In this paper, we present a comprehensive overview of the research of the deep structure of rocky celestial bodies using solid tidal parameters, including tidal Love numbers and tidal quality factor. First, the basic theory of solid tides, tidal parameters, and viscoelastic models are introduced, and the relationship between the internal structural parameters of the celestial bodies and their solid tidal response is established. This is followed by a review and summary of existing work using solid tide parameters to study the internal structure of the rocky celestial bodies like Mercury, Venus, Mars, and the Moon. Examples include the study of the viscoelastic structure at the base of the lunar mantle using tidal parameters, and the use of tidal parameters to improve the uncertainty of the Martian core radius demonstrate that using solid tidal parameters is an effective method of constraining the deep structure of the celestial bodies. We further provide the contribution of high-precision observations to be acquired by future missions to the study of internal structure. However, there still are some problems in study the internal structure of celestial bodies by solid tidal parameters. For instance, the variability of dissipation strength between different viscoelastic models, the mismatch between short-period experimental data and macroscopic long-period theoretical calculations of viscoelastic models, and so on. We also discuss and analyzes these problems and provides a vision of future research direction.

To determine the effects of explicit instruction (EI) and potential moderators in second/foreign language (L2) teaching, this study meta-analyzed 28 primary reports (a total of 67 unique samples, N = 3754). The main results show that EI was significantly effective in facilitating L2 development, with effect sizes ranging from moderate to large magnitudes (d = 1.07 and 0.81 for within-and between-group contrasts, respectively). Moderator analyses show that EI type, practice type, delivery mode, length and intensity of treatment, the type of outcome measures, as well as the reporting practices of the validity and reliability of outcome measures moderated differentially the effects of EI. The findings offer important pedagogical implications for teacher-practitioners to enhance the efficacy and efficiency of EI.

Abstract Background Metabolic dysfunction-associated steatotic liver disease(MASLD) is the most common cause of chronic liver disease. Clinical evidences have demonstrated the link between MASLD and the increased risk of cardiovascular disease (CVD) development. We aimed to investigate the relationship between Life’s Essential 8 (LE8), an enhanced approach to assessing cardiovascular health(CVH), and MASLD. Methods Data were extracted from the National Health and Nutrition Examination Survey (NHANES) in 2017–2020 cycles. MASLD was assessed by the latest diagnostic criteria. LE8 scores (range 0–100) were obtained from measurements based on American Heart Association definitions, divided into health factor and health behavior scores. Multivariable logistic and restricted cubic spline models were used to assess the associations. Results 5646 participants were included based on the inclusion and exclusion criteria, 2616 (46.33%) participants were diagnosed with MASLD. After adjusting for confounding variables, higher LE8 scores were associated with a lower risk of MASLD (OR = 0.19, 95%CI 0.17–0.21; P

The increasing prevalence of chronic diseases globally poses major challenges to the health of societies and individuals. Managing chronic diseases requires long-term treatment and monitoring, placing demands on patients' lifestyles. With the aging of the population and changes in lifestyle, chronic disease prevention and control are becoming more and more important. In recent years, as scientific and technological innovation in the field of healthcare develops in depth, and the application of artificial intelligence in healthcare has gradually become one of the important strategic directions of the country, the traditional method of chronic disease management relies too much on the offline communication between the doctor and the patient, which leads to the doctor not being able to maintain long-term and effective communication and follow up with the patient, and the patient may not be able to be detected and monitored by the doctor in a timely manner when his or her condition changes. In addition, the traditional chronic disease management approach is usually a generalized approach that fails to adequately consider the individual differences of each patient. Given the limitations of traditional chronic disease management methods, this study aims to provide more convenient and efficient primary care services using intelligent robots. Through personalized health management plans, assisted medical diagnosis, and timed medication reminders, the intelligent robot is committed to improving patients' quality of life, reducing the pressure on healthcare resources, and promoting the development of intelligent healthcare management globally.

Abstract Purpose To report a rare variant of the posterior septal artery (PSA), which supplies blood to the posterior mucosa of the contralateral nasal septum. Case report A 31‐year‐old female patient underwent suture removal 14 days after septoplasty and developed left‐sided epistaxis 6 h after suture removal. To safely and effectively relieve the patient from epistaxis, the cauterization of the left PSA was performed under general anesthesia. However, 24 h after the first surgical hemostasis, the patient experienced epistaxis again in the right nasal cavity. We have reviewed the patient's sinus computed tomography again and found a rare variant of PSA, which is the right‐sided PSA passing through a bony canal in the left‐sided nasal septum. Discussion The variant of PSA well explained the failure of the first hemostatic surgery. Therefore, we again performed a cauterization of the right‐sided PSA, after which the patient recovered and no further epistaxis occurred. Conclusion When cauterization of PSA is used to manage posterior epistaxis, it is necessary to pay attention to the possible variation in PSA.

Drought stress significantly affects crop productivity. Carotenoids are essential photosynthetic pigment for plants, bacteria, and algae, with signaling and antioxidant functions. Lutein is a crucial branch product in the carotenoid synthesis pathway, which effectively improves the stress tolerance of higher plants. lycopene cyclase, a central enzyme for lutein synthesis, holds great significance in regulating lutein production. This research establishes a correlation between lutein content and stress resistance by measuring the drought resistance and lutein content of various cotton materials. To identify which crucial genes are associated with lutein, the lycopene cyclase family (LCYs) was analyzed. The research found that LCYs form a highly conserved family divided into two subfamilies, LCY-ε (lycopene ε-cyclase) and LCY-β (lycopene β-cyclase). Most members of the LCY family contain photoresponsive elements and abscisic acid elements. qRT-PCR demonstrates showed that most genes responded positively to drought stress, and GhLCYε-3 was expressed significantly differently under drought stress. Virus-induced gene silencing (VIGS) assay showed that the content of GhLCYε-3 was significantly increased with MDA and PRO, and the contents of chlorophyll and lutein were significantly decreased in pYL156 plants. The decrease in GhLCYε-3 expression is speculated to lead to reduced lutein content in vivo, resulting in the accumulation of reactive oxygen species (ROS) and decreased drought tolerance. This research enriched the understanding of LCY gene family and lutein function, and provided a new reference for cotton planting in arid areas. Synopsis: Lycopene cyclase plays an important role in enhancing the ability of scavenging ROS and drought resistance of plants.

Background: Diabetic neuropathy (DN) is one of the common chronic complications, leading to limb disability and increased risks of hospitalization and mortality. Traditional Chinese medicine (TCM) has been commonly applied in Taiwan as an adjunctive treatment to ameliorate diabetes-associated chronic complications, including neuropathy. Aim: We aimed to investigate whether the clinical treatment of DN combined with TCM can reduce the associated hospitalization and mortality using the National Health Insurance Research Database (NHIRD) of Taiwan. Methods: We selected 1,152 patients with DN who received TCM treatment as the study cohort group, and 4,940 patients with DN who did not receive TCM treatment from Taiwan NHIRD were further matched 1:1 for sex, age, and index year as the comparison cohort group. Cox proportional hazards analysis was performed to compare hospitalization and mortality during a mean follow-up period of 15 years. Results: A total of 687/225 enrolled patients (29.82%/9.77%) had hospitalization/mortality, including 298/97 in the TCM group (25.87%/8.42%) and 389/128 in the comparison group (33.77%/11.11%). Cox proportional hazard regression analysis showed a lower rate of hospitalization and mortality for patients in the TCM group (adjusted hazard ratio [HR] of 0.434, 95 confidence interval [CI] =0.172–0.798, P < 0.001; adjusted HR of 0.689, 95 CI = 0.372–0.981, P = 0.039). The Kaplan–Meier analysis showed that the cumulative risk of hospitalization and mortality in the study and comparison cohort groups was significantly different (log-rank P < 0.001 and P = 0.007, respectively). Conclusion: Our results suggest that the application of TCM might be beneficial for patients with DN to lower the risks of hospitalization and mortality; however, further prospective cohort studies are still required to confirm our observations.

Abstract In the General Next-to-Minimal Supersymmetric Standard Model (GNMSSM), singlet particles may form a secluded sector of dark matter (DM), in which Singlino-like DM could achieve the observed relic abundance through various channels such as χ ~ 1 0 χ ~ 1 0 → h s h s $$ {\overset{\sim }{\chi}}_1^0{\overset{\sim }{\chi}}_1^0\to {h}_s{h}_s $$ , A s A s , h s A s , where h s and A s represent singlet-dominated CP-even and CP-odd Higgs bosons. We provide analytical formulas for both the spin-independent and spin-dependent cross sections of Singlino DM scattering with nucleons, illustrating their dependence on the model’s parameters in a clear manner. We also present analytic expressions for the annihilation cross sections of these three important channels. Based on these preparations, we conducted Bayesian analyses of the GNMSSM and concluded that the theory significantly favored Singlino-dominated DM over Bino-like DM across a much broader range of parameters. The combined results from our numerical analyses and the formulas distinctly highlight crucial aspects of DM physics within the GNMSSM.

Abstract Background Prediabetes mellitus (PreDM) is a high-risk state for developing type 2 diabetes mellitus (T2DM) and often goes undiagnosed, which is closely associated with obesity and characterized by insulin resistance that urgently needs to be treated. Purpose To obtain a better understanding of the biological processes associated with both "spleen-dampness" syndrome individuals and those with dysglycaemic control at its earliest stages, we performed a detailed metabolomic analysis of individuals with various early impairments in glycaemic control, the results can facilitate clinicians’ decision making and benefit individuals at risk. Methods According to the diagnostic criteria of TCM patterns and PreDM, patients were divided into 4 groups with 20 cases, patients with syndrome of spleen deficiency with dampness encumbrance and PreDM (PDMPXSK group), patients with syndrome of dampness-heat in the spleen and PreDM (PDMSRYP group), patients with syndrome of spleen deficiency with dampness encumbrance and normal blood glucose (NDMPXSK group), and patients with syndrome of dampness-heat in the spleen and normal blood glucose (NDMSRYP group). Plasma samples from patients were collected for clinical index assessment and untargeted metabolomics using liquid chromatography-mass spectrometry. Results Among patients with the syndrome of spleen deficiency with dampness encumbrance (PXSK), those with PreDM (PDMPXSK group) had elevated levels of 2-hour post-load blood glucose (2-h PG), glycosylated hemoglobin (HbA1c), high-density lipoprotein cholesterol (HDL-C), and systolic blood pressure (SBP) than those in the normal blood glucose group (NDMPXSK group, P

Abstract Eosinophils, traditionally associated with allergic phenomena, play a pivotal role in inflammatory responses. Despite accumulating evidence suggesting their pro-inflammatory function upon activation, the underlying mechanisms governing eosinophil activation remain incompletely characterized. In this study, we investigate the local activation of pulmonary and colon eosinophils within the inflammatory microenvironment. Leveraging transcriptional sequencing, we identify TGF-β as a putative regulator of eosinophil activation, leading to the secretion of granule proteins, including peroxidase. Genetic deletion of TGF-β receptors on eosinophils resulted in the inhibition of peroxidase synthesis, affirming the significance of TGF-β signaling in eosinophil activation. Using models of HDM-induced asthma and DSS-induced colitis, we demonstrate the indispensability of TGF-β-driven eosinophil activation in both disease contexts. Notably, while TGF-β signaling did not significantly influence asthmatic inflammation, its knockout conferred protection against experimental colitis. This study delineates a distinct pattern of eosinophil activation within inflammatory responses, highlighting the pivotal role of TGF-β signaling in regulating eosinophil behavior. These findings deepen our comprehension of eosinophil-related pathophysiology and may pave the way for targeted therapeutic approaches in allergic and inflammatory diseases.

Abstract Purpose Investigate the clinical characteristics of splenomegaly secondary to acute pancreatitis (SSAP) and construct a nomogram prediction model based on Lasso-Logistic regression. Methods A retrospective case-control study was conducted to analyze the laboratory parameters and computed tomography (CT) imaging of acute pancreatitis (AP) patients recruited at Xuanwu Hospital from December 2014 to December 2021. Lasso regression was used to identify risk factors, and a novel nomogram was developed. The performance of the nomogram in discrimination, calibration, and clinical usefulness was evaluated through internal validation. Results The prevalence of SSAP was 9.2% (88/950), with the first detection occurring 65(30, 125) days after AP onset. Compared with the control group, the SSAP group exhibited a higher frequency of persistent respiratory failure, persistent renal failure, infected pancreatic necrosis, and severe AP, along with an increased need for surgery and longer hospital stay (P

Abstract Paternal genome elimination (PGE) is an intriguing but poorly understood reproductive strategy in which females are typically diploid, but males lose paternal genomes. Paternal genome heterochromatin (PGH) occurs in arthropods with germline PGE, such as the mealybug, coffee borer beetles, and booklice. Here, we present evidence that PGH initially occurs during early embryo development at around 15 h post-mating (hpm) in the cotton mealybug, Phenacoccus solenopsis Tinsley. Transcriptome analysis followed by qPCR validation indicated that six histone lysine methyltransferase (KMT) genes are predominantly expressed in adult females. We knocked down these five genes through dsRNA microinjection. We found that downregulation of two KMT genes, PsEZH2-X1 and PsEHMT1, resulted in a decrease of heterochromatin-related methylations, including H3K27me1, H3K27me3, and H3K9me3 in the ovaries, fewer PGH male embryos, and reduced male offspring. For further confirmation, we obtained two strains of transgenic tobacco highly expressing dsRNA targeting PsEZH2-X1 and PsEHMT1, respectively. Similarly, fewer PGH embryos and fewer male offspring were observed when feeding on these transgenic tobacco plants. Overall, we present evidence that PsEZH2-X1 and PsEHMT1 have essential roles in male embryo survival by regulating PGH formation in cotton mealybugs.

Objective: To investigate the effect of Bifidobacterium animalis subsp. lactis XLTG11 (XLTG11) on immune function and intestinal flora in cyclophosphamide (CTX)-immunosuppressed mice. Methods: Altogether 60 mice were randomly divided into five groups: blank, model, low-dose, medium-dose and high-dose XLTG11 groups. The blank group was injected intraperitoneally with normal saline from day 1 to 3, and the other groups 100 μL of CTX solution (40 mg/kg) to establish an immunocompromised mouse model. From day 4 to 30, the low-, medium- and high-dose XLTG11 groups were given 0.2 mL of XLTG11 suspensions at doses of 2.5 × 106, 2.5 × 107 and 2.5 × 108 CFU/animal, respectively, and both blank and model groups 0.2 mL of normal saline/animal. Body mass, immune organ index, delayed-type metamorphosis, proliferation of splenic lymphocytes, T-lymphocyte subpopulation, natural killer (NK) cell activity, phagocytic activity of peritoneal macrophages, cytokine levels, intestinal flora structure, and short-chain fatty acids (SCFA) were detected in each group of mice. Results: XLTG11 increased the immune organ index, foot-plantar thickness, splenic lymphocyte proliferation, T lymphocyte subsets CD4+ and CD8+, NK cell activity and macrophage phagocytosis activity, and cellular immune factors (interleukin (IL)-6, IL-10, IL-1β and interferon (IFN)-γ) in immunosuppressed mice. In addition, XLTG11 alleviated intestinal tissue damage caused by CTX, regulated the intestinal flora and increased intestinal SCFA (acetic, propionic and butyric acid) levels. Conclusion: XLTG11 could significantly enhance the immune function and regulate the intestinal flora of mice.

This study assessed the effects of the addition of biochar prepared at 700 °C with different dosages on the anaerobic digestion of food waste. The biochar addition at a concentration of 10.0 g/L increased the cumulative methane yield by 128%, and daily methane production was also significantly promoted. The addition of biochar derived from poplar sawdust significantly increased the relative abundance of dominant bacteria for anaerobic digestion by 85.54–2530% and promoted the degradation of refractory organic matter and the transfer of materials between the hydrolysis and acid production stages. Further analysis has demonstrated that Bathyarchaeia and hydrogenotrophic methanogens were enriched by the biochar addition. Meanwhile, the relative abundances of functional genes, including C5-branched dibasic acid metabolism, and pyruvate metabolism, were increased by 11.38–26.27%. The relative abundances of genes related to major amino acid metabolism, including histidine metabolism, lysine biosynthesis, and phenylalanine, tyrosine, and tryptophan biosynthesis, were increased by 11.96–15.71%. Furthermore, the relative abundances of genes involved in major replication and repair were increased by 14.76–22.76%, and the major folding, sorting, degradation, and translation were increased by 14.47–19.95%, respectively. The relative abundances of genes related to major membrane transport and cell motility were increased by 10.02 and 83.09%, respectively. HIGHLIGHTS Different dosages of biochar in the anaerobic digestion process of food waste were studied.; 16S rRNA gene sequencing and PCR were used to analyze bacterial and archaeal domains.; The addition of biochar has promoted the improvement of anaerobic digestion performance, e.g. the improvement of methane production capacity, the increase of anaerobic digestion-dominant bacterial communities, and the abundance of functional genes.;

Abstract The mortality of ovarian cancer (OC) has long been the highest among gynecological malignancies. Although OC is considered to be an immunogenic tumor, the effect of immunotherapy is not satisfactory. The immunosuppressive microenvironment is one reason for this, and the absence of recognized effective antigens for vaccines is another. Chemotherapy, as one of the most commonly used treatment for OC, can produce chemotherapy-associated antigens (CAAs) during treatment and show the effect of in situ vaccine. Herein, we designed an antigen capture nano-vaccine NP-TP1@M-M with tumor targeting peptide TMTP1 and dendritic cell (DC) receptor mannose assembled on the surface and adjuvant monophosphoryl lipid A (MPLA) encapsulated in the core of poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles. PLGA itself possessed the ability of antigen capture. TMTP1 was a tumor-homing peptide screened by our research team, which held extensive and excellent tumor targeting ability. After these modifications, NP-TP1@M-M could capture and enrich more tumor-specific antigens after chemotherapy, stimulate DC maturation, activate the adaptive immunity and combined with immune checkpoint blockade to maximize the release of the body’s immune potential, providing an eutherapeutic strategy for the treatment of OC.

Abstract Diagnosing individuals with autism spectrum disorder (ASD) accurately faces great challenges in clinical practice, primarily due to the data's high heterogeneity and limited sample size. To tackle this issue, the authors constructed a deep graph convolutional network (GCN) based on variable multi‐graph and multimodal data (VMM‐DGCN) for ASD diagnosis. Firstly, the functional connectivity matrix was constructed to extract primary features. Then, the authors constructed a variable multi‐graph construction strategy to capture the multi‐scale feature representations of each subject by utilising convolutional filters with varying kernel sizes. Furthermore, the authors brought the non‐imaging information into the feature representation at each scale and constructed multiple population graphs based on multimodal data by fully considering the correlation between subjects. After extracting the deeper features of population graphs using the deep GCN(DeepGCN), the authors fused the node features of multiple subgraphs to perform node classification tasks for typical control and ASD patients. The proposed algorithm was evaluated on the Autism Brain Imaging Data Exchange I (ABIDE I) dataset, achieving an accuracy of 91.62% and an area under the curve value of 95.74%. These results demonstrated its outstanding performance compared to other ASD diagnostic algorithms.

Abstract Background A cross-sectional population-based survey in the Beichen district of Tianjin was conducted to estimate the prevalence of dry eye disease (DED) among the population over 50 years old with Dry Eye Workshop (DEWS) II and Chinese expert consensus (CEC) criteria. Methods A total of 5791 subjects over 50 years old were enrolled. Ocular surface disease index (OSDI) questionnaire, lipid layer thickness (LLT), partial blink ratio (PBR), fluorescein tear film breakup time (FBUT), Schirmer I test (SIT), fluorescein staining, meibomian gland dropout, meibomian gland expression scores (MES) and quantity scores (MQS) was assessed. Additionally, basic information, weight, disease history, living habits, anxiety, and depression condition were collected. Results According to the CEC, the prevalence of DED was 39.0%, whereas 44.0% based on DEWS II. The prevalence of DED increased with age and was substantially greater among women (41.1%, 95% CI, 39.5-42.6%) than males (35.1%, 95% CI, 33.1 -37.2%) (p

Abstract Background The fruit of Phyllanthus emblica L., a traditional medicine in China and India, is used to treat diabetes mellitus. Its water extract (WEPE) has demonstrated hypoglycemic effects in diabetic rats, but its mechanisms on glucose utilization and insulin resistance in skeletal muscle remain unclear. Therefore, this study aims to investigate the effects and underlying mechanisms of WEPE on glucose utilization and insulin resistance using C2C12 myotubes. Methods Effects of WEPE on glucose uptake, GLUT4 translocation, and AMPK and AKT phosphorylation were investigated in C2C12 myotubes and palmitate-treated myotubes. An AMPK inhibitor and siRNA were used to explore the mechanisms of WEPE. Glucose uptake was determined using a 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake assay, and protein expression and GLUT4 translocation were assessed via western blotting. Results In normal myotubes, WEPE significantly stimulated glucose uptake and GLUT4 translocation to the plasma membrane at concentrations of 125 and 250 µg/mL. This was accompanied by an increase in the phosphorylation of AMPK and its downstream targets. However, both compound C and AMPK siRNA blocked the WEPE-induced GLUT4 translocation and glucose uptake. Moreover, pretreatment with STO-609, a calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ) inhibitor, inhibited WEPE-induced AMPK phosphorylation and attenuated the WEPE-stimulated glucose uptake and GLUT4 translocation. In myotubes treated with palmitate, WEPE prevented palmitate-induced insulin resistance by enhancing insulin-mediated glucose uptake and AKT phosphorylation. It also restored the insulin-mediated translocation of GLUT4 from cytoplasm to membrane. However, these effects of WEPE on glucose uptake and GLUT4 translocation were blocked by pretreatment with compound C. Conclusions WEPE significantly stimulated basal glucose uptake though CaMKKβ/AMPK pathway and markedly ameliorated palmitate-induced insulin resistance by activating the AMPK pathway in C2C12 myotubes.

For traditional spent fuel shielding materials, due to physical and chemical defects and cost constraints, they have been unable to meet the needs. Therefore, this paper carries out the first discussion on the application and performance of bismuth in neutron shielding by establishing Monte Carlo simulation on the neutron flux model of shielded spent fuel. Firstly, functional fillers such as bismuth oxide, lead oxide, boron oxide, gadolinium oxide and tungsten oxide are added to the matrices to compare the shielding rates of aluminum alloy matrix and silicone rubber matrix. The shielding rate of silicone rubber mixture is higher than aluminum alloy mixture, reaching more than 56%. The optimal addition proportion of bismuth oxide and lead oxide is 30%, and the neutron radiation protection efficiency reaches 60%. Then, the mass attenuation coefficients of bismuth oxide, lead oxide, boron oxide, gadolinium oxide and tungsten oxide in silicone rubber matrix are simulated with the change of functional fillers proportion and neutron energy. This simulation result shows that the mixture with functional fillers has good shielding performance for low energy neutrons, but poor shielding effect for high energy neutrons. Finally, in order to further evaluate the possibility of replacing lead oxide with bismuth oxide as shielding material, the half-value layers and various properties of bismuth oxide and lead oxide are compared. The results show that the shielding properties of bismuth oxide and lead oxide are basically the same, and the mechanical properties, heat resistance, radiation resistance and environmental protection of bismuth oxide are better than that of lead oxide. Therefore, in the case of neutron source strengths in the range of 0.01–6 MeV and secondary gamma rays produced below 2.5 MeV, bismuth can replace lead in neutron shielding applications.

A high-resolution meteorological dataset (≤10 km) over the Tibetan Plateau (TP) is the foundation for investigating and predicting the weather and climate over Asia. The TP Subregional Dynamical Downscaling (TPSDD) dataset is a newly developed high-spatial-temporal resolution gridded dataset for land‒air exchange processes and lower atmospheric structure studies over the whole TP region, taking the climate characteristics of each TP subregion into consideration. The dataset spans from 1981 to 2020, covering the TP with a temporal resolution of 2 hr and spatial resolution of 10 km. Meteorological elements of the dataset include near-surface land–air exchange parameters, such as downward/upward longwave/shortwave radiation flux, sensible heat flux, latent heat flux, etc. In addition, the vertical distributions of 3-dimensional wind, temperature, humidity, and pressure from the surface to the lower stratosphere are also included. Independent evaluations were conducted to verify the performance of the TPSDD dataset by comparing TPSDD/reanalysis with surface and vertical observations through the calculation of statistical parameters. The results demonstrate the accuracy and superiority of this dataset against reanalysis data, which provides great potential for future climate change research.

Abstract Background The introduction of non-native species is a primary driver of biodiversity loss in freshwater ecosystems. The redclaw crayfish (Cherax quadricarinatus) is a freshwater species that exhibits tolerance to hypoxic stresses, fluctuating temperatures, high ammonia concentration. These hardy physiological characteristics make C. quadricarinatus a popular aquaculture species and a potential invasive species that can negatively impact tropical and subtropical ecosystems. Investigating the genomic basis of environmental tolerances and immune adaptation in C. quadricarinatus will facilitate the development of management strategies of this potential invasive species. Results We constructed a chromosome-level genome of C. quadricarinatus by integrating Nanopore and PacBio techniques. Comparative genomic analysis suggested that transposable elements and tandem repeats drove genome size evolution in decapod crustaceans. The expansion of nine immune-related gene families contributed to the disease resistance of C. quadricarinatus. Three hypoxia-related genes (KDM3A, KDM5A, HMOX2) were identified as being subjected to positive selection in C. quadricarinatus. Additionally, in vivo analysis revealed that upregulating KDM5A was crucial for hypoxic response in C. quadricarinatus. Knockdown of KDM5A impaired hypoxia tolerance in this species. Conclusions Our results provide the genomic basis for hypoxic tolerance and immune adaptation in C. quadricarinatus, facilitating the management of this potential invasive species. Additionally, in vivo analysis in C. quadricarinatus suggests that the role of KDM5A in the hypoxic response of animals is complex.

Abstract Background Extracellular matrix (ECM) stiffness is closely related to the progress of diabetic cardiomyopathy (DCM) and the response of treatment of DCM to anti-diabetic drugs. Dapagliflozin (Dapa) has been proven to have cardio-protective efficacy for diabetes and listed as the first-line drug to treat heart failure. But the regulatory relationship between ECM stiffness and treatment efficacy of Dapa remains elusive. Materials and methods This work investigated the effect of ECM stiffness on DCM progression and Dapa efficacy using both in vivo DCM rat model and in vitro myocardial cell model with high glucose injury. First, through DCM rat models with various levels of myocardial injury and administration with Dapa treatment for four weeks, the levels of myocardial injury, myocardial oxidative stress, expressions of AT1R (a mechanical signal protein) and the stiffness of myocardial tissues were obtained. Then for mimicking the stiffness of myocardial tissues at early and late stages of DCM, we constructed cell models through culturing H9c2 myocardial cells on the polyacrylamide gels with two stiffness and exposed to a high glucose level and without/with Dapa intervention. The cell viability, reactive oxygen species (ROS) levels and expressions of mechanical signal sensitive proteins were obtained. Results The DCM progression is accompanied by the increased myocardial tissue stiffness, which can synergistically exacerbate myocardial cell injury with high glucose. Dapa can improve the ECM stiffness-induced DCM progression and its efficacy on DCM is more pronounced on the soft ECM, which is related to the regulation pathway of AT1R-FAK-NOX2. Besides, Dapa can inhibit the expression of the ECM-induced integrin β1, but without significant impact on piezo 1. Conclusions Our study found the regulation and effect of biomechanics in the DCM progression and on the Dapa efficacy on DCM, providing the new insights for the DCM treatment. Additionally, our work showed the better clinical prognosis of DCM under early Dapa intervention.

Abstract Pazopanib (PAZ), an oral multi-tyrosine kinase inhibitor, demonstrates promising cytostatic activities against various human cancers. However, its clinical utility is limited by substantial side effects and therapeutic resistance. We developed a nanoplatform capable of delivering PAZ for enhanced anti-breast cancer therapy. Nanometer-sized PAZ@Fe-MOF, compared to free PAZ, demonstrated increased anti-tumor therapeutic activities in both syngeneic murine 4T1 and xenograft human MDA-MB-231 breast cancer models. High-throughput single-cell RNA sequencing (scRNAseq) revealed that PAZ@Fe-MOF significantly reduced pro-tumorigenic M2-like macrophage populations at tumor sites and suppressed M2-type signaling pathways, such as ATF6-TGFBR1-SMAD3, as well as chemokines including CCL17, CCL22, and CCL24. PAZ@Fe-MOF reprogramed the inhibitory immune microenvironment and curbed tumorigenicity by blocking the polarization of M2 phenotype macrophages. This platform offers a promising and new strategy for improving the cytotoxicity of PAZ against breast cancers. It provides a method to evaluate the immunological response of tumor cells to PAZ-mediated treatment.

Abstract As a vital material utilized in energy storage capacitors, dielectric ceramics have widespread applications in high-power pulse devices. However, the development of dielectric ceramics with both high energy density and efficiency at high temperatures poses a significant challenge. In this study, we employ high-entropy strategy and band gap engineering to enhance the energy storage performance in tetragonal tungsten bronze-structured dielectric ceramics. The high-entropy strategy fosters cation disorder and disrupts long-range ordering, consequently regulating relaxation behavior. Simultaneously, the reduction in grain size, elevation of conductivity activation energy, and increase in band gap collectively bolster the breakdown electric strength. This cascade effect results in outstanding energy storage performance, ultimately achieving a recoverable energy density of 8.9 J cm−3 and an efficiency of 93% in Ba0.4Sr0.3Ca0.3Nb1.7Ta0.3O6 ceramics, which also exhibit superior temperature stability across a broad temperature range up to 180 °C and excellent cycling reliability up to 105. This research presents an effective method for designing tetragonal tungsten bronze dielectric ceramics with ultra-high comprehensive energy storage performance.

Green-grey infrastructures' implementation has progressed significantly in cities around the globe for sustainable stormwater management. This review study conducted on green-grey infrastructures' optimization represented recent research trends, existing research status, possible study gaps, and future research directions and recommendations needed for further improvements. The findings show that the research on green-grey infrastructures has got significant attention recently (after 2012) because of accessibility to computational resources and the development of hydrological-hydraulic models and optimization algorithms. Furthermore, research on green-grey infrastructures is mostly conducted in ten countries including China, USA and Iran ranked in the first three places, respectively, delivering their advantages to other countries with the essential awareness and knowledge. Most previous studies considered particular quantitative and qualitative optimization objectives and these studies were conducted at smaller retrofitting scales, therefore, future studies need to expand their scope towards socio-ecological objectives with consideration of larger study areas or multi-stage planning, designing, and implementation. Moreover, future research is recommended to consider stakeholders’ participation in preliminary planning and designing stages for the successful implementation of sustainable stormwater management approaches. Lastly, the surrogate-based optimization approaches instead of traditional optimization methods can overcome the burden of computational time and resources in future. HIGHLIGHTS A critical review on the urban green-grey infrastructure development.; State-of-the-art analysis of urban stormwater systems.; Discussion and recommendation for optimal development of green-grey infrastructures.;

Abstract Malignant pleural effusion (MPE) is a common occurrence in advanced cancer and is often linked with a poor prognosis. Eosinophils were reported to involve in the development of MPE. However, the role of eosinophils in MPE remains unclear. To investigate this, we conducted studies using both human samples and mouse models. Increased eosinophil counts were observed in patients with MPE, indicating that the higher the number of eosinophils is, the lower the LENT score is. In our animal models, eosinophils were found to migrate to pleural cavity actively upon exposure to tumor cells. Intriguingly, we discovered that a deficiency in eosinophils exacerbated MPE, possibly due to their anti-tumor effects generated by modifying the microenvironment of MPE. Furthermore, our experiments explored the role of the C-C motif chemokine ligand 11 (CCL11) and its receptor C-C motif chemokine receptor 3 (CCR3) in MPE pathology. As a conclusion, our study underscores the protective potential of eosinophils against the development of MPE, and that an increase in eosinophils through adoptive transfer of eosinophils or increasing their numbers improved MPE.

Abstract Objective Chronological age (CAge), biological age (BAge), and accelerated age (AAge) are all important for aging‐related diseases. CAge is a known risk factor for benign prostatic hyperplasia (BPH); However, the evidence of association of BAge and AAge with BPH is limited. This study aimed to evaluate the association of CAge, Bage, and AAge with BPH in a large prospective cohort. Method A total of 135,933 males without BPH at enrolment were extracted from the UK biobank. We calculated three BAge measures (Klemera–Doubal method, KDM; PhenoAge; homeostatic dysregulation, HD) based on 16 biomarkers. Additionally, we calculated KDM‐BAge and PhenoAge‐BAge measures based on the Levine method. The KDM‐AAge and PhenoAge‐AAge were assessed by the difference between CAge and BAge and were standardized (mean = 0 and standard deviation [SD] = 1). Cox proportional hazard models were applied to assess the associations of CAge, Bage, and AAge with incident BPH risk. Results During a median follow‐up of 13.150 years, 11,811 (8.690%) incident BPH were identified. Advanced CAge and BAge measures were associated with an increased risk of BPH, showing threshold effects at a later age (all P for nonlinearity 2 SD) had a significantly elevated BPH risk with hazard ratio (HR) of 1.115 (95% CI, 1.000–1.223) for KDM‐AAge and 1.180 (95% CI, 1.068–1.303) for PhenoAge‐AAge, respectively. For PhenoAge‐AAge, subgroup analysis of the accelerated aging group showed an increased HR of 1.904 (95% CI, 1.374–2.639) in males with CAge

BackgroundN-hexane has been a widely used solvent in industrial production, but it is volatile at room temperature and can be accumulated in the body, and its prolonged occupational exposure may lead to serious chronic diseases in workers. ObjectiveTo use four risk assessment models to evaluate the health risk levels of n-hexane-exposed workers, discuss the applicability of the four models in the health risk assessment of n-hexane exposure, and make an important supplement to the health risk assessment of n-hexane in China. MethodsIn 2022, a total of 167 jobs (1724 workers) exposed to n-hexane in 85 manufacturing enterprises in Jiangsu Province were selected, and a cross-sectional study was conducted and included questionnaire surveys and evaluation of on-site air n-hexane of each job. Subsequently, the China’s classification standards of occupational hazards at workplaces (China model), U.S. Environmental Protection Agency (EPA) model, Singapore semi-quantitative risk assessment model (Singapore model), and the International Council on Mining and Metals (ICMM) model were applied to the quantitative, semi-quantitative, and qualitative assessments of the occupational health risk level of n-hexane-exposed workers. ResultsAll job’s 8-h time-weighted average concentrations (CTWA) of n-hexane were within the national occupational exposure limits (OELs). The results of the China model graded all jobs as relatively harmless. The Singapore model graded all jobs as low risk, except that two monitoring sites of adhesive jobs were assessed as medium risk. The ICMM quantitative model evaluated all jobs as intolerable for n-hexane airborne exposure, while the matrix method evaluated all jobs as low risk. The U.S. EPA model identified five sites involving painting, printing, and adhesive jobs as high risk and the other jobs as low risk. ConclusionInconsistent grading results are observed by using the four models for the occupational health risk assessment of n-hexane exposure, that is, harmless for all jobs by China model, while medium and high risks by Singapore model and U.S. EPA model. Therefore, we recommend to combine the Singapore model and the U.S. EPA model with the China model to assess the occupational risk of n-hexane-exposed workers by considering actual concentrations of exposure.

Abstract Heparan sulfate (HS) is degraded in lysosome by a series of glycosidases. Before the glycosidases can act, the terminal glucosamine of HS must be acetylated by the integral lysosomal membrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT). Mutations of HGSNAT cause HS accumulation and consequently mucopolysaccharidosis IIIC, a devastating lysosomal storage disease characterized by progressive neurological deterioration and early death where no treatment is available. HGSNAT catalyzes a unique transmembrane acetylation reaction where the acetyl group of cytosolic acetyl-CoA is transported across the lysosomal membrane and attached to HS in one reaction. However, the reaction mechanism remains elusive. Here we report six cryo-EM structures of HGSNAT along the reaction pathway. These structures reveal a dimer arrangement and a unique structural fold, which enables the elucidation of the reaction mechanism. We find that a central pore within each monomer traverses the membrane and controls access of cytosolic acetyl-CoA to the active site at its luminal mouth where glucosamine binds. A histidine-aspartic acid catalytic dyad catalyzes the transfer reaction via a ternary complex mechanism. Furthermore, the structures allow the mapping of disease-causing variants and reveal their potential impact on the function, thus creating a framework to guide structure-based drug discovery efforts.

Abstract GPRC5D is an atypical Class C orphan G protein-coupled receptor. Its high expression on the surface of multiple myeloma cells has rendered it an attractive target for therapeutic interventions, including monoclonal antibodies, CAR-T cells, and T-cell engagers. Despite its therapeutic potential, the insufficient understanding regarding of the receptor’s structure and antibody recognition mechanism has impeded the progress of effective therapeutic development. Here, we present the structure of GPRC5D in complex with a preclinical-stage single-chain antibody (scFv). Our structural analysis reveals that the GPRC5D presents a close resemblance to the typical Class C GPCRs in the transmembrane region. We identify a distinct head-to-head homodimer arrangement and interface mainly involving TM4, setting it apart from other Class C homo- or hetero-dimers. Furthermore, we elucidate the binding site engaging a sizable extracellular domain on GPRC5D for scFv recognition. These insights not only unveil the distinctive dimer organization of this unconventional Class C GPCR but also hold the potential to advance drug development targeting GPRC5D for the treatment of multiple myeloma.

Enterovirus D68 (EV-D68) infection causes severe acute respiratory infection and severe neurological complications, such as acute flaccid myelitis (AFM), in children. However, although EV-D68 has pandemic potential, no effective drugs or vaccines are currently clinically available. Furthermore, EV-D68 infection-induced inflammatory response and cell death are not fully understood. In this study, we demonstrated that several inflammatory cytokines were upregulated in a multiplicity of infection (MOI) dependent manner in EV-D68-infected human rhabdomyosarcoma (RD) cells. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) confirmed that tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), C-C motif chemokine ligand-5 (CCL-5), and CXC motif chemokine ligand-5 (CXCL-5) mRNA levels were highly upregulated after EV-D68 infection. IL-1β processing and maturation mediated by caspase-8 was inhibited by the caspase-8 inhibitor Z-IETD-FMK. EV-D68 infection activates caspase-8 to mediate IL-1β maturation and secretion. Additionally, EV-D68 activated cell death-related proteins such as caspase-3, poly (ADP-ribose) polymerase 1 (PARP-1), phosphorylation of Mixed Lineage Kinase domain-like protein (pMLKL), and gasdermin E (GSDME). Thus, EV-D68 infection activates caspase-8, which triggers the necroptosis and apoptosis pathways. Overall, our data suggest that caspase-8 activation is associated with the inflammatory response and cell death in EV-D68-infected RD cells. This mechanism represents a novel target for the treatment of EV-D68 infection by inhibiting caspase-8 activation.

Abstract Background The present study evaluated whether the lack of histone deacetylase 4 (HDAC4) increases endoplasmic reticulum stress-induced chondrocyte apoptosis by releasing activating transcription factor 4 (ATF4) in human osteoarthritis (OA) cartilage degeneration. Methods Articular cartilage from the tibial plateau was obtained from patients with OA during total knee replacement. Cartilage extracted from severely damaged regions was classified as degraded cartilage, and cartilage extracted from a relatively smooth region was classified as preserved cartilage. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining was used to detect chondrocyte apoptosis. HDAC4, ATF4, and C/EBP homologous protein (CHOP) expression levels were measured using immunohistochemistry staining and real-time quantitative PCR. Chondrocytes were transfected with HDAC4 or HDAC4 siRNA for 24 h and stimulated with 300 µM H2O2 for 12 h. The chondrocyte apoptosis was measured using flow cytometry. ATF4, CHOP, and caspase 12 expression levels were measured using real-time quantitative PCR and western blotting. Male Sprague-Dawley rats (n = 15) were randomly divided into three groups and transduced with different vectors: ACLT + Ad-GFP, ACLT + Ad-HDAC4-GFP, and sham + Ad-GFP. All rats received intra-articular injections 48 h after the operation and every three weeks thereafter. Cartilage damage was assessed using Safranin O staining and quantified using the Osteoarthritis Research Society International score. ATF4, CHOP, and collagen II expression were detected using immunohistochemistry, and chondrocyte apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Results The chondrocyte apoptosis was higher in degraded cartilage than in preserved cartilage. HDAC4 expression was lower in degraded cartilage than in preserved cartilage. ATF4 and CHOP expression was increased in degraded cartilage. Upregulation of HDAC4 in chondrocytes decreased the expression of ATF4, while the expression of ATF4 was increased after downregulation of HDAC4. Upregulation of HDAC4 decreased the chondrocyte apoptosis under endoplasmic reticulum stress, and chondrocyte apoptosis was increased after downregulation of HDAC4. In a rat anterior cruciate ligament transection OA model, adenovirus-mediated transduction of HDAC4 was administered by intra-articular injection. We detected a stronger Safranin O staining with lower Osteoarthritis Research Society International scores, lower ATF4 and CHOP production, stronger collagen II expression, and lower chondrocyte apoptosis in rats treated with Ad-HDAC4. Conclusion The lack of HDAC4 expression partially contributes to increased ATF4, CHOP, and endoplasmic reticulum stress-induced chondrocyte apoptosis in OA pathogenesis. HDAC4 attenuates cartilage damage by repressing ATF4-CHOP signaling-induced chondrocyte apoptosis in a rat model of OA.

Abstract Background Vitamin D was shown to directly exert a protective effect on diabetic kidney disease (DKD) in our previous study. However, whether it has an effect on perirenal adipose tissue (PRAT) or the intestinal flora and its metabolites (trimethylamine N-oxide, TMAO) is unclear. Methods DKD mice were received different concentrations of 1,25-(OH)2D3 for 2 weeks. Serum TNF-α levels and TMAO levels were detected. 16S rRNA sequencing was used to analyze gut microbiota. qPCR was used to detect the expression of TLR4, NF-Κb, PGC1α, and UCP-1 in kidney and adipose tissue. Histological changes in kidney and perirenal adipose tissue were observed using HE, PAS, Masson and oil red staining. Immunofluorescence and immunohistochemistry were used to detect the expression of VDR, PGC1α, podocin, and UCP-1 in kidney and adipose tissue. Electron microscopy was used to observe the pathological changes in the kidney. VDR knockout mice were constructed to observe the changes in the gut and adipose tissue, and immunofluorescence and immunohistochemistry were used to detect the expression of UCP-1 and collagen IV in the kidney. Results 1,25-(OH)2D3 could improve the dysbiosis of the intestinal flora of mice with DKD, increase the abundance of beneficial bacteria, decrease the abundance of harmful bacteria, reduce the pathological changes in the kidney, reduce fat infiltration, and downregulate the expression of TLR4 and NF-κB in kidneys. The serum TMAO concentration in mice with DKD was significantly higher than that of the control group, and was significantly positively correlated with the urine ACR. In addition, vitamin D stimulated the expression of the surface markers PGC1α, UCP-1 and VDR in the PRAT in DKD mice, and TMAO downregulated the expression of PRAT and renal VDR. Conclusions The protective effect of 1,25-(OH)2D3 in DKD mice may affect the intestinal flora and its related metabolite TMAO on perirenal fat and kidneys.